데이터 상품 상세검색

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치료제 데이터셋

치료제 데이터셋

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● 데이터 상품명 치료제 데이터셋 ● 데이터 상품 부제 COVID-19의 임상 관련 치료제 데이터셋 ● 데이터 상품 요약 인용지수 상위 의학저널에 게재된 COVID-19의 치료제에 관련된 의학 학술논문 데이터 ● 키워드 데이터셋 상품 정보 ■ 상품 설명 및 특징 - 의학논문의 저자 키워드, 초록, 제목 등에서 추출한 키워드에 키워드 속성, 대역어, 키워드 출처, 논문 DOI, 저자, 발행연월, 논문URL, 저널명, 저널 ISSN, 발행기관, Impact Factor의 정보를 매핑한 데이터 ■ 컬럼(속성) 정보 - 키워드명: 키워드 - 키워드속성: 키워드 성격 - 키워드출처: 키워드 출현 위치 - 키워드대역어: 자체 보유 의학사전 및 구글번역기에 의한 대역어 - 논문DOI명: 키워드 출현 논문의 DOI - 논문제목: 키워드 출현 논문의 제목 - 논문저자: 키워드 출현 논문의 저자 - 논문발행연월: 키워드 출현 논문의 발행연월 - 논문초록: 키워드 출현 논문의 초록 - 논문URL: 키워드 출현 논문의 URL - 저널ISSN명: 키워드 출현 논문의 저널 ISSN - 저널제목: 키워드 출현 논문의 저널명 - 저널발행기관명: 키워드 출현 논문의 발행기관명 ● 연관 데이터셋 상품 정보 ■ 상품 설명 및 특징 - 특정 키워드의 연관 키워드를 co-occurrence기법과 Latent Semantic Algorithm에 의해 추출한 데이터셋 ■ 컬럼(속성) 정보 - 키워드명: 키워드 - 키워드속성: 키워드의 성격 - 연관키워드명: 키워드와 연관된 키워드 - 연관키워드 속성: 연관키워드의 속성 - 연관중요도: 동의여 여부와 동시출현수를 지표로 하는 중요도 ● 기간 및 범위 - 2014년 5월 ~ 2022년 12월 ● 활용 예제 - 특정 주제에 해당되는 키워드의 속성별, 저널별, 연도별, 저자별 추이 - 키워드의 연관어를 속성별, 저널별, 연도별, 저자별 분석

샘플정보
ID
카테고리ID
카테고리명
키워드명
키워드속성
대체키워드명
키워드출처
키워드대역어
논문ID
논문DOI명
논문제목
논문저자
논문발행연월
논문유형
논문출처
논문초록
논문URL
저널ID
저널ISSN명
저널제목
저널발행기관명
저널ImpactFactor명
117412 899 치료제 Mild to moderate COVID-19 Virus mild to moderate COVID-19 abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117413 899 치료제 mild to moderate symptoms Symptom mild to moderate symptom abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117414 899 치료제 moderate Term moderate abstract 중등도 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117415 899 치료제 Moderate COVID-19 Disease moderate covid-19 abstract 보통 코비드 -19 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117416 899 치료제 MONITOR Term MONITOR abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117417 899 치료제 mouth Term mouth abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117490 899 치료제 ARMS Organ ARMS abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117420 899 치료제 no significant difference Action no significant difference abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117421 899 치료제 objective Term objective abstract abnormality 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117422 899 치료제 oral Term oral abstract 입안 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117423 899 치료제 Oropharyngeal Term oropharyngeal abstract 인두 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117424 899 치료제 participant Patient participant abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117425 899 치료제 Participants Patient participant abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117426 899 치료제 Patient Term patient abstract 환자 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117427 899 치료제 patients receiving placebo Patient patients receiving placebo abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117428 899 치료제 Phase 2 Term phase 2 title 2상 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117429 899 치료제 Placebo Term placebo abstract 위약 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117430 899 치료제 placebo-controlled clinical trial Term placebo-controlled clinical trial abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117491 899 치료제 article Term article abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117431 899 치료제 placebo group Patient placebo group abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117432 899 치료제 platform Term platform abstract 편평 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117433 899 치료제 Point Term point abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117434 899 치료제 polymerase chain Molecule polymerase chain abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117435 899 치료제 polymerase chain reaction Term polymerase chain reaction abstract 중합효소 연쇄 반응 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117436 899 치료제 positive Action positive abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117437 899 치료제 primary end point Term primary end point abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117438 899 치료제 proportion Term proportion abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117439 899 치료제 Randomized Term randomized abstract 무작위 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117440 899 치료제 randomized clinical trial Term randomized clinical trial abstract 무작위 임상 시험 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117441 899 치료제 Randomly Term randomly abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117442 899 치료제 receive Action receive abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117443 899 치료제 receiving Action receiving abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117444 899 치료제 Registration Term registration abstract 등록 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117445 899 치료제 Relevance Term relevance abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117446 899 치료제 reported Action reported abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117447 899 치료제 respiratory Term respiratory abstract 호흡기 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117448 899 치료제 respiratory sample Term respiratory sample abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117449 899 치료제 Respiratory samples Term respiratory sample abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117450 899 치료제 Result Term result abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117451 899 치료제 Safe Term safe abstract 금고 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117452 899 치료제 sample collection Term sample collection abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117453 899 치료제 Sample size Term sample size abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117454 899 치료제 SAR-CoV-2 Term sar-cov-2 abstract SAR-COV-2 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117495 899 치료제 controlled trials Term controlled trial abstract 통제 된 시험 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117455 899 치료제 SARS-CoV-2 Virus sars-cov-2 title,abstract 제2형 중증급성호흡기증후군 코로나바이러스 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117456 899 치료제 SARS-CoV-2 clearance Term sars-cov-2 clearance abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117457 899 치료제 setting Term setting abstract abnormality 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117458 899 치료제 shedding Term shedding title 흘림 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117459 899 치료제 significant effect Action significant effect abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117460 899 치료제 significantly Action significantly abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117461 899 치료제 Standard of care Term standard of care abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117462 899 치료제 statistically Term statistically abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117463 899 치료제 Symptom Symptom symptom abstract 증상 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117464 899 치료제 symptom duration Term symptom duration abstract 증상 지속 시간 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117507 899 치료제 evaluate Action evaluate abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117465 899 치료제 symptom resolution Term symptom resolution abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117466 899 치료제 Symptoms Symptom symptom abstract 증상 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117467 899 치료제 the placebo group Patient the placebo group abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117468 899 치료제 therapy Treatment therapy abstract 치료 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117469 899 치료제 treat Action treat abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117470 899 치료제 Treatment Treatment treatment abstract 치료 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117471 899 치료제 treatment for COVID-19 Treatment treatment for COVID-19 abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117472 899 치료제 treatment groups Patient treatment group abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117473 899 치료제 Trial Term trial abstract 시험 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117474 899 치료제 trial participants Patient trial participant abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117475 899 치료제 Tuft Term tuft abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117476 899 치료제 vaccination Term vaccination abstract 백신 접종 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117477 899 치료제 Viral Term viral abstract 바이러스의 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117478 899 치료제 viral clearance Term viral clearance abstract 바이러스 제거 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117479 899 치료제 viral shedding Term viral shedding abstract 바이러스 흘림 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117480 899 치료제 was collected Action was collected abstract None 7751 10.1001/jamanetworkopen.2021.44942 Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19 A Phase 2 Randomized Clinical Trial Dana M. Cairns@@@Dorothy Dulko@@@Jeffrey K. Griffiths@@@Yoav Golan@@@Theodora Cohen@@@Ludovic Trinquart@@@Lori Lyn Price@@@Kirthana R. Beaulac@@@Harry P. Selker 202202 Article PMC This randomized clinical trial compares the efficacy of niclosamide vs placebo in respiratory clearance of SARS-CoV-2 among patients with mild to moderate COVID-19. Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated. Meaning This study did not find a significant effect of niclosamide on decreasing the contagious period of SAR-CoV-2 infection. Importance Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase?polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 ( P =?.37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, ?2.6 [95% CI, ?7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P =?.31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P =?.82). Conclusions and Relevance In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04399356 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829666/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117481 899 치료제 95% CI Term 95% CI abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117482 899 치료제 95% CIs Term 95% cis abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117483 899 치료제 accounted Action accounted abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117485 899 치료제 adverse event Term adverse event abstract 부작용 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117486 899 치료제 adverse events Term adverse event abstract 부작용 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117487 899 치료제 AEs Term ae abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117488 899 치료제 analyzed Action analyzed abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117497 899 치료제 COVID-19 vaccination Treatment covid-19 vaccination abstract Covid-19 백신 접종 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117498 899 치료제 COVID-19 vaccine Term covid-19 vaccine abstract 코로나19 백신 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117499 899 치료제 COVID-19 vaccines Drug covid-19 vaccine abstract 코로나19 백신 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
123068 899 치료제 non-infectiousness Term non-infectiousness abstract None 8165 10.1007/s15010-020-01530-4 An approach to lifting self-isolation for health care workers with prolonged shedding of SARS-CoV-2 RNA H. Laferl@@@H. Kelani@@@T. Seitz@@@B. Holzer@@@I. Zimpernik@@@A. Steinrigl@@@F. Schmoll@@@C. Wenisch@@@F. Allerberger 202010 Original Paper PMC Purpose According to the European Public Health Authority guidance for ending isolation in the context of COVID-19, a convalescent healthcare worker (HCW) can end their isolation at home and resume work upon clinical improvement and two negative RT-PCR tests from respiratory specimens obtained at 24-h intervals at least 8 days after the onset of symptoms. However, convalescent HCWs may shed SARS-CoV-2 viral RNA for prolonged periods. Methods 40 healthy HCWs off work because of ongoing positive RT-PCR results in combined nasopharyngeal (NP) and oropharyngeal (OP) swabs following SARS-CoV-2 infection were invited to participate in this study. These HCWs had been in self-isolation because of a PCR-confirmed SARS-CoV-2 infection. NP and OP swabs as well as a blood sample were collected from each participant. RT-PCR and virus isolation was performed with each swab sample and serum neutralization test as well as two different ELISA tests were performed on all serum samples. Results No viable virions could be detected in any of 29 nasopharyngeal and 29 oropharyngeal swabs taken from 15 long-time carriers. We found SARSCoV- 2 RNA in 14/29 nasopharyngeal and 10/29 oropharyngeal swabs obtained from screening 15 HCWs with previous COVID-19 up to 55 days after symptom onset. Six (40%) of the 15 initially positive HCWs converted to negative and later reverted to positive again according to their medical records. All but one HCW, a healthy volunteer banned from work, showed the presence of neutralizing antibodies in concomitantly taken blood samples. Late threshold cycle (Ct) values in RT-PCR [mean 37.4; median 37.3; range 30.8?41.7] and the lack of virus growth in cell culture indicate that despite the positive PCR results no infectivity remained. Conclusion We recommend lifting isolation if the RT-PCR Ct-value of a naso- or oropharyngeal swab sample is over 30. Positive results obtained from genes targeted with Ct-values > 30 correspond to non-viable/noninfectious particles that are still detected by RT-PCR. In case of Ct-values lower than 30, a blood sample from the patient should be tested for the presence of neutralizing antibodies. If positive, non-infectiousness can also be assumed. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538033/ 657 0300-8126 Infection Heidelberg : Springer Heidelberg.
117500 899 치료제 COVID-19 vaccine trial Term COVID-19 vaccine trial abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117501 899 치료제 COVID-19 vaccine trials Term COVID-19 vaccine trial abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117502 899 치료제 database Term database abstract 데이터베이스 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117503 899 치료제 data extraction Term data extraction abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117504 899 치료제 dose Compound dose abstract 선량 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117505 899 치료제 drug trials Treatment drug trial abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117508 899 치료제 event Term event abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117509 899 치료제 Evidence Term evidence abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117510 899 치료제 extraction Term extraction abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117511 899 치료제 fatigue Symptom fatigue abstract 피로 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117512 899 치료제 finding Term finding abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117513 899 치료제 first dose Term first dose abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117514 899 치료제 frequencies Term frequency abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117515 899 치료제 Frequency Term frequency abstract 주파수 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117516 899 치료제 groups Patient group abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117517 899 치료제 headache Symptom headache abstract 두통 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117518 899 치료제 Importance Term importance abstract None 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
117519 899 치료제 independent Term independent abstract abnormality 7760 10.1001/jamanetworkopen.2021.43955 Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis Julia W. Haas@@@Friederike L. Bender@@@Sarah Ballou@@@John M. Kelley@@@Marcel Wilhelm@@@Franklin G. Miller@@@Winfried Rief@@@Ted J. Kaptchuk 202201 Meta-Analysis PMC This systematic review and meta-analysis investigates the frequency of adverse events in placebo groups compared with that in vaccine groups in COVID-19 vaccine trials. Key Points Question What was the frequency of adverse events (AEs) in the placebo groups of COVID-19 vaccine trials? Findings In this systematic review and meta-analysis of 12 articles including AE reports for 45?380 trial participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second. Significantly more AEs were reported in the vaccine groups, but AEs in placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first COVID-19 vaccine dose and 52% after the second dose. Meaning This study found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial; this finding should be considered in public vaccination programs. Importance Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy. Objective To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups. Data Sources For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021. Study Selection Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers. Data Extraction and Synthesis Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models. Main Outcomes and Measures The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs. Results Twelve articles with AE reports for 45?380 participants (22?578 placebo recipients and 22?802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, ?0.47; 95% CI, ?0.54 to ?0.40; P <?.001; standardized mean difference, ?0.26; 95% CI, ?0.30 to ?0.22) and large after the second dose (OR, ?1.36; 95% CI, ?1.86 to ?0.86; P <?.001; standardized mean difference, ?0.75; 95% CI, ?1.03 to ?0.47). Conclusions and Relevance In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767431/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
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